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APOBEC3F and APOBEC3G inhibit HIV-1 DNA integration by different mechanisms

Jean L Mbisa1, Wei Bu, Vinay K Pathak

  • 1HIV Drug Resistance Program, National Cancer Institute at Frederick, P.O. Box B, Building 535, Room 334, Frederick, MD 21702-1201, USA.

Journal of Virology
|March 12, 2010
PubMed

Insights

APOBEC3F (A3F) and APOBEC3G (A3G) inhibit HIV-1 replication by mutating viral DNA. A3F is more potent than A3G at blocking viral DNA integration through distinct mechanisms involving DNA processing and binding affinity.

Area of Science:

  • Virology
  • Molecular Biology
  • Immunology

Background:

  • APOBEC3F (A3F) and APOBEC3G (A3G) are host restriction factors that inhibit HIV-1 replication.
  • Their antiviral activity involves cytidine deamination, leading to lethal mutations in the viral genome.
  • Previous research showed A3G blocks viral DNA transfer and provirus establishment.

Purpose of the Study:

  • To investigate if A3F interferes with HIV-1 provirus formation similarly to A3G.
  • To compare the mechanisms by which A3F and A3G inhibit HIV-1 proviral DNA integration.
  • To determine the role of the catalytic domain and DNA binding affinity in the distinct functions of A3F and A3G.

Main Methods:

  • Southern blot analysis to examine viral cDNA processing.
  • Assessing inhibition of viral DNA synthesis and integration.
  • Evaluating the impact of functional catalytic domains on antiviral activity.
  • Measuring binding affinity of A3F and A3G to viral DNA templates.

Main Results:

  • Both A3F and A3G inhibit HIV-1 DNA synthesis and integration, with A3F being more potent in preventing integration.
  • A3G causes a 6-bp extension at the 3'-LTR U5 end, hindering integration.
  • A3F inhibits integration by reducing 3' processing at both U5 and U3 ends.
  • A functional C-terminal catalytic domain is more critical for A3G than A3F.
  • A3F exhibits greater binding affinity for viral 3'-LTR dsDNA than A3G.

Conclusions:

  • A3F and A3G employ distinct mechanisms to prevent HIV-1 DNA integration.
  • Differences in target specificity and/or dsDNA binding affinity contribute to their distinct antiviral functions.
  • A3F is a more potent inhibitor of HIV-1 provirus formation than A3G due to its unique mechanism of action.

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